Solution structure of an arabinonucleic acid (ANA)/RNA duplex in a chimeric hairpin:: comparison with 2′-fluoro-ANA/RNA and DNA/RNA hybrids
Solution structure of an arabinonucleic acid (ANA)/RNA duplex in a chimeric hairpin:: comparison with 2′-fluoro-ANA/RNA and DNA/RNA hybrids
复制标题
DOI：
10.1093/nar/29.21.4284
复制
发表时间：
2001-11-01
影响因子：
14.9
通讯作者：
Damha, MJ
中科院分区：
文献类型：
--
作者：
Denisov, AY;Noronha, AM;Damha, MJ
RNA和阿拉伯核酸（ANA）的杂交体以及2'-氟ANA类似物（2' f -ANA）最近被证明是RNase H酶的底物。尽管RNase H与双链RNA结合，但这种双链不发生切割。因此，了解ANA/RNA杂交体的结构可能有助于未来反义寡核苷酸类似物的设计。在这项研究中，我们确定了ANA/RNA和DNA/RNA发夹双链的核磁共振溶液结构，并将它们与最近发表的2'F-ANA/RNA发夹双链的结构进行了比较。我们在这里证明了ANA/RNA发夹干的RNA核苷酸的糖采用C3‘-末端（北，a型）构象，而ANA链的糖采用’刚性' O4'-末端（东）糖袋。DNA/RNA发夹茎的DNA链具有弹性，但平均DNA/RNA发夹结构参数接近ANA/RNA和2'F-ANA/RNA发夹参数。ANA/RNA、2'F-ANA/RNA和DNA/RNA螺旋的小凹槽宽度为9.0 +/- 0.5埃，介于a型和b型双链之间。这些结果合理化了ANA/RNA和2'F-ANA/RNA杂交体诱导RNase H活性的能力。
Hybrids of RNA and arabinonucleic acid (ANA) as well as the 2'-fluoro-ANA analog (2'F-ANA) were recently shown to be substrates of the enzyme RNase H. Although RNase H binds to double-stranded RNA, no cleavage occurs with such duplexes. Therefore, knowledge of the structure of ANA/RNA hybrids may prove helpful in the design of future antisense oligonucleotide analogs. In this study, we have determined the NMR solution structures of ANA/RNA and DNA/RNA hairpin duplexes and compared them to the recently published structure of a 2'F-ANA/RNA hairpin duplex. We demonstrate here that the sugars of RNA nucleotides of the ANA/RNA hairpin stem adopt the C3'-endo (north, A-form) conformation, whereas those of the ANA strand adopt a 'rigid' O4'-endo (east) sugar pucker. The DNA strand of the DNA/RNA hairpin stem is flexible, but the average DNA/RNA hairpin structural parameters are close to the ANA/RNA and 2'F-ANA/RNA hairpin parameters. The minor groove width of ANA/RNA, 2'F-ANA/RNA and DNA/RNA helices is 9.0 +/- 0.5 Angstrom, a value that is intermediate between that of A- and B-form duplexes. These results rationalize the ability of ANA/RNA and 2'F-ANA/RNA hybrids to elicit RNase H activity.